Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells

Yong Liu, Maurizio Chiriva-Internati, Changxuan You, Rongcheng Luo, Hong You, C. Krishna Prasad, Fabio Grizzi, Everardo Cobos, Vicki Klimberg, Helen Kay, Jawahar L. Mehta, Paul L. Hermonat

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Antigen-targeted immunotherapy is an emerging treatment for breast cancer. However, useful breast cancer antigens are only found in a subset of cancer patients. BA46, also known as lactadherin, is a membrane-associated glycoprotein that is expressed in most breast cancer cells but not in general hematopoietic cell populations. Moreover, it is much more difficult to generate CTLs against self-antigens. We wished to determine if the use of recombinant adeno-associated virus (rAAV) type 2 vectors for gene-loading of dendritic cells (DCs) could generate rapid, effective cytotoxic T lymphocytes (CTLS) against BA46. We were able to demonstrate that AAV/BA46/Neo-loading of DCs resulted in: (1) BA46 expression in DCs, (2) chromosomal integration of the AAV/BA46/Neo vector within DCs, (3) strong, rapid BA46-specific, MHC class I-restricted CTLs in only 1 week, (4) T-cell populations with significant interferon-γ (IFN-γ) expression but low IL-4 expression, (5) high CD80 and CD86 expression in DCs, and (6) high CD8:CD4 and CD8:CD56 T cell ratios. These data suggest that rAAV-loading of DCs may be useful for immunotherapeutic protocols against self-antigens in addition to viral antigens and that the BA46 antigen is potentially appropriate for cell-mediated immunotherapeutic protocols addressing ductal breast cancer.

Original languageEnglish (US)
Pages (from-to)304-312
Number of pages9
JournalCancer Gene Therapy
Volume12
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Keywords

  • Adeno-associated virus
  • BA46
  • Breast cancer
  • Cytotoxic T lymphocyte
  • Dendritic cell
  • Immunology

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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